Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21665-8
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Funding
- Victorian Government [GNT2002073]
- Medical Research Future Fund (MRFF) [GNT2002073]
- ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
- NHMRC [APP1149990, GNT1162760]
- NHMRC-EU collaborative award [APP1115828]
- European Union Horizon 2020 Research and Innovation Programme [681137]
- Jack Ma Foundation
- A2 Milk Company
- Australian Government Department of Health
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The study compared the immunogenicity of spike proteins (S) and receptor binding domain (RBD) in SARS-CoV-2 vaccines in mice and macaques, finding that S was highly immunogenic in mice while RBD was comparatively poor. Both S and RBD vaccines were similarly immunogenic in macaques, inducing serological neutralising activity exceeding convalescent human levels.
SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation. Current vaccine strategies for SARS-CoV-2 focus on eliciting neutralising antibodies to the spike protein (S), but differences in immunogenicity of full-length S versus receptor binding domain (RBD) only aren't fully understood. Here, the authors show immunogenicity of different prime-boost strategies with S and/or RBD in mice and macaques.
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